Sedative hypnotic agents are widely used for the induction and maintenance of general anesthesia, for sedation during surgical or diagnostic procedures and for sedation of patients in intensive care. Commonly assigned U.S. patent application Ser. No. 10/350,624 discloses the novel phenylacetic acid ester [4-[(N,N-diethylcarbamoyl)methoxy]-3-ethoxyphenyl]acetic acid propyl ester
as a useful short-acting sedative hypnotic agent. Among other properties, [4-[(N,N-diethylcarbamoyl)methoxy]-3-ethoxyphenyl]acetic acid propyl ester is expected to be pharmacokinetically responsive, providing shorter and more predictable duration of action than other sedative hypnotic agents.
Agents for sedation and anesthesia are frequently administered by injection, a form of administration for which the agents need to be formulated in an aqueous medium. [4-[(N,N-Diethylcarbamoyl)methoxy]-3-ethoxyphenyl]acetic acid propyl ester, however, is an oleaginous compound, which is poorly, if, at all soluble in aqueous media. The preparation of poorly soluble medicinal compounds for intravenous administration has been the subject of considerable investigation, but remains a significant challenge in the development of new therapeutic agents. For example, U.S. Pat. No. 4,711,902 discloses certain sparingly soluble medicinal compounds can be formulated as lipid emulsions using esters of medium chain length fatty acids as the lipid solvent. Propofol, 2,6-diisopropylphenol, is another oleaginous agent used for sedation and anesthesia. Propofol is currently provided commercially in the U.S. by AstraZeneca as Diprivan® Injectable Emulsion, at a 1% concentration in a soybean oil containing emulsion.
The lower the concentration of drug, the higher the ratio of lipid solvent to drug, and hence the higher the amount of lipids provided to the patient, with an attendant risk of hyperlipidemia, to produce the same therapeutic effect. It would be desirable to provide a formulation of [4-[(N,N-diethylcarbamoyl)methoxy]-3-ethoxyphenyl]acetic acid propyl ester suitable for injection at a sufficiently high drug concentration using ingredients appropriate for administration by injection. Furthermore, for use in practice, it would be desirable, for the formulation of [4-[(N,N-diethylcarbamoyl)methoxy]-3-ethoxyphenyl]acetic acid propyl ester to be sufficiently stable to permit storage.